Patent GB-1220599-A (GB)
Title: New furazan derivatives, processes for their production and compositions containing them
IPC: C07C259/14
Filed: 1968-02-06
Abstract: 1,220,599. 3 - Amino - 4 - (alkylphenyl). furazans. J. R. GEIGY A.G. 6 Feb., 1968 [7 Feb., 1967], No. 5896/68. Heading C2C. Novel 3 - amino - 4 - (alkylphenyl) - furazans of the general formula wherein R 1  is a hydrogen atom or a C 1-5  alkyl group and R 2  is a C 1-5  alkyl group in the o- or m-position, are prepared (a) by reaction of an alkylphenyl-glyoxal-alkoxime of the general formula or an alkali metal salt thereof with 2 mol. equivalents of hydroxylamine; (b) by reaction of an alkylphenyl-glyoxylonitrile oxime of the general formula or an alkali metal salt thereof with 2 mol. equivalents of hydroxylamine; (c) by cyclization of a 2-(alkylphenyl)-glyoxylamide oxime derivative of the general formula wherein X 1 , X 2  and X 3  are hydrogen atoms or carboxylic acyl radicals, and optional simultaneous hydrolysis; (d) by hydrolysis of a 4 - (alkylphenyl) - furazan - 3 - carbamic acid ester or a 4-(alkylphenyl)-3-acylamino-furazan of the general formula wherein X 3 <SP>1</SP> is a carboxylic acyl, alkoxycarbonyl or aryloxycarbonyl radical; (e) by reaction of a 4-(alkylphenyl)-5-nitrosoimidazole derivative of the general formula wherein R 4  is a hydrogen atom or a low alkyl group, with hydroxylamine hydrochloride; (f) by heating in a strong mineral acid a 3- (alkylbenzoyl - 1 - oxa - 2,4 - diazole oxime derivative of the general formula wherein R 4  is a C 1-5  alkyl group; (g) by subjection of a 4-(alkylphenyl)-furazan-3-carboxamide of the general formula to a Hofmann degradation; and (h) by reduction of a 3-amino-4-(alkylphenyl)-furoxan of the general formula Pharmaceutical compositions having central nervous system depressant, anti-convulsive and muscle-relaxing activity comprise, as active ingredient, a 3-amino-4-(alkylphenyl)- furazan of the first general formula above in combination with a pharmaceutically acceptable diluent or carrier therefor. Alkylphenyl-glyoxalaldoximes of the second general formula above are prepared by reaction of an alkyl-substituted acetophenone with butyl nitrite in the presence of ethanolic sodium ethylate. Alkylphenyl-glyoxylonitrile oximes of the third general formula above are prepared by reaction of an alkylphenyl-acetonitrile with butyl nitrite in the presence of ethanolic sodium ethylate. 4-(Alkylphenyl-3- alkanoylamido-furazans of the fifth general formula above wherein X 3 <SP>1</SP> is an alkanoyl radical are prepared by reaction of an alkylsubstituted phenacyl chloride or bromide simultaneously with gaseous ammonia and an alkanoylamide, reaction of the resulting 2- alkyl - 4 - (alkylphenyl) - imidazole with butyl nitrite in the presence of ethanolic sodium ethylate and treatment of the 2-alkyl-4-(alkylphenyl) - 5 - nitroso - imidazole thus obtained with hydroxylamine. 3 - Amino - 4 - (alkylphenyl-furoxans of the ninth general formula above are prepared by oxidation of a 1-amino- 2-(alkylphenyl)-glyoxime with an aqueous solution of a halogen or with a potassium ferricyanide solution, or by reaction of an alkylphenyl-glyoxime with ammonia and potassium ferricyanide in an aqueous solution, and may be converted to their isomers of the tenth general formula above by heating or ultra-violet radiation. α - (3,4 - Xylyl) - α - 0 - benzoyl - # -  benzoylamino-glyoxime is prepared by reaction of α - amino - # - (3,4 - xylyl) - glyoxime with benzoyl chloride α - (3,4 - Xylyl) - α - O- acetyl - # - acetamidoglyoxime is prepared by reaction of the sodium salt of 3,4-xylyl-glyoxalaldoxime with hydroxylamine hydrochloride, treatment of the resulting 3,4-xylylglyoxime with dinitrogen tetroxide, reaction of the 3,4 - xylyl - glyoxylonitrile - oxide oxime so produced with ammonia and reaction of the resulting α - (3,4 - xylyl) - # - amino - glyoxime with acetic anhydride. 1-Amino-2-(o-tolyl)- glyoxime is prepared by reaction of o-tolylglyoxylonitrile oxime with hydroxylamine.